Chen Cunrong, Hong Huashan, Chen Lianglong, Shi Xiaoyun, Chen Ying, Weng Qinyong
Department of Critical Care Medicine, Union Hospital, Fujian Medical University.
Tohoku J Exp Med. 2014 Jun;233(2):89-94. doi: 10.1620/tjem.233.89.
MicroRNAs (miRNAs) are involved in the regulation of a variety of biological processes, such as inflammation. Dysregulation of miRNAs have been implicated in many human disease, including cardiovascular diseases. Polymorphisms in miRNA genes may affect the miRNA biogenesis and function, and thus cause changes in the expression of thousands of genes. The aim of this study was to examine whether miRNA polymorphisms (miR-146a rs2910164, miR-149 rs71428439, miR-196a2 rs11614913, miR-218 rs11134527, and miR-499 rs3746444) contribute to the risk for the development of myocardial infarction (MI). Five miRNA polymorphisms were genotyped in a total of 1808 subjects composed of 919 MI patients and 889 control individuals. The GG genotype of rs3746444 was found to be associated with a significantly increased risk of MI (recessive model, adjusted OR = 1.710, 95% CI: 1.058-2.763, P = 0.029). Although the CC genotype of rs2910164 significantly increased the risk of MI under dominant and additive models (P < 0.05), this difference disappeared after adjustment for age, sex, blood pressure, triglycerides, total cholesterol, HDL, LDL and diabetes. In addition, when rs3746444 and rs2910164 were evaluated together by the number of putative high-risk alleles, we found an increased risk of MI for subjects carrying 3-4 risk alleles (3-4 risk alleles vs. 0-1 risk allele, adjusted OR = 1.580, 95% CI: 1.069-2336, P = 0.022; 3-4 risk alleles vs. 0-2 risk allele, adjusted OR = 1.513, 95% CI: 1.031-2.219, P = 0.034). These findings indicate that miR-499 rs3746444 and miR-146a rs2910164 may represent novel markers of MI susceptibility.
微小RNA（miRNA）参与多种生物学过程的调控，如炎症反应。miRNA的失调与许多人类疾病有关，包括心血管疾病。miRNA基因的多态性可能影响miRNA的生物合成和功能，从而导致数千个基因表达的变化。本研究的目的是检验miRNA多态性（miR-146a rs2910164、miR-149 rs71428439、miR-196a2 rs11614913、miR-218 rs11134527和miR-499 rs3746444）是否会增加心肌梗死（MI）发生的风险。在总共1808名受试者中对5种miRNA多态性进行了基因分型，其中包括919名MI患者和889名对照个体。发现rs3746444的GG基因型与MI风险显著增加相关（隐性模型，校正OR = 1.710，95%CI：1.058 - 2.763，P = 0.029）。虽然rs2910164的CC基因型在显性和加性模型下显著增加了MI风险（P < 0.05），但在对年龄、性别、血压、甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白和糖尿病进行校正后，这种差异消失了。此外，当通过假定的高危等位基因数量对rs3746444和rs2910164进行联合评估时，我们发现携带3 - 4个风险等位基因的受试者发生MI的风险增加（3 - 4个风险等位基因与0 - 1个风险等位基因相比，校正OR = 1.580，95%CI：1.069 - 2.336，P = 0.022；3 - 4个风险等位基因与0 - 2个风险等位基因相比，校正OR = 1.513，95%CI：1.031 - 2.219，P = 0.034）。这些发现表明，miR-499 rs3746444和miR-146a rs2910164可能是MI易感性的新标志物。
